We are seeking matching funds for our tuberculosis (fl3)vaccine efforts, involving both pre-clinical and clinical studies. Specifically, these include the optimization of vaccine constructs and delivery systems in animal models to maximize protective efficacy. We will, using the priority Mtb antigens we have identified, produce poly-proteins with high expression levels in recombinant systems suitable for manufacture and use these protein antigens with state-of-the-art adjuvants, already tested in the clinic, along with delivery systems chosen to maximize T cell responses. We will focus vaccine studies in the guinea pig and primate systems, as well as use mice to characterize immune responses induced by the experimental vaccines. Finally, we will perform a clinical trial with a poly-protein construct consisting of three Mtb antigens produced as a single protein, formulated with AS2, an adjuvant shown to be safe and effective in the clinic. The purpose of the trial is to show safety and immunogenicity of a promising vaccine in normal human subjects.